title: Targeted delivery of siRNA against hepatitis B virus by preS1 peptide molecular ligand.
abstract: OBJECTIVE
  For chronic hepatitis B virus (HBV) infection, the effects of current therapies are limited. RNA interference of virus-specific genes has emerged as a potential antiviral mechanism. However, a suitable delivery vector is still to be developed. We studied a novel vector transferring siRNA targeting hepatic cells in vivo and in vitro in order to find a new way to cure HBV-related live diseases.
  
  
  METHODS
  The preS1-9Arg ligand was used to deliver siRNA to HepG2 and to HepG2 2.2.15 cells. To validate the antiviral efficacy in vivo, a HBV viremic animal model was established by s.c. inoculation of HepG2 2.2.15 tumor cells in nude mice. The minimal retardation effect on the migration of siRNA was detected by gel electrophoresis to confirm the combination and the optimal ratio. Hepatitis B surface antigen (HBsAg) levels were detected by semiquantitatively enzyme-linked immunosorbent assay RNA levels were quantified with quantitative real-time polymerase chain reaction and protein levels were determined with immunoblots and immunohistochemistry.
  
  
  RESULTS
  PreS1-9Arg peptide strongly combined and transferred siRNA into HepG2 cells. PreS1-9Arg-siRNA molecular conjugate effectively reduced the production of HBsAg and HBV DNA without liver toxicity in vitro and in vivo.
  
  
  CONCLUSIONS
  The results indicated that preS1-9Arg may be a potential novel vector to deliver siRNA targeting liver cells.
authors.affiliation: Department of Laboratory Medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Huang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Yi
authors.forename: Sufen
authors.initials: S
authors.lastname: Zhu
authors.forename: Weixian
authors.initials: W
authors.lastname: Chen
keywords: RNA interference; hepatitis B virus; molecular ligand; preS1